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Identification of metabolic phenotypes in childhood obesity by 1H NMR metabolomics of blood plasma.

ABSTRACT: Aim:To identify the plasma metabolic profile associated with childhood obesity and its metabolic phenotypes. Materials & methods:The plasma metabolic profile of 65 obese and 37 normal-weight children was obtained using proton NMR spectroscopy. NMR spectra were rationally divided into 110 integration regions, which reflect relative metabolite concentrations, and were used as statistical variables. Results:Obese children show increased levels of lipids, N-acetyl glycoproteins, and lactate, and decreased levels of several amino acids, ?-ketoglutarate, glucose, citrate, and cholinated phospholipids as compared with normal-weight children. Metabolically healthy children show lower levels of lipids and lactate, and higher levels of several amino acids and cholinated phospholipids, as compared with unhealthy children. Conclusion:This study reveals new valuable findings in the field of metabolomics and childhood obesity. Although validation should be performed, the proof of principle looks promising and justifies a deeper investigation of the diagnostic possibilities of proton NMR metabolomics in follow-up studies. Trial registration: NCT03014856. Registered January 9, 2017.

SUBMITTER: Bervoets L

PROVIDER: S-EPMC6060399 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Identification of metabolic phenotypes in childhood obesity by <sup>1</sup>H NMR metabolomics of blood plasma.

Bervoets Liene L Massa Guy G Guedens Wanda W Reekmans Gunter G Noben Jean-Paul JP Adriaensens Peter P

Future science OA 20180523 6

<h4>Aim</h4>To identify the plasma metabolic profile associated with childhood obesity and its metabolic phenotypes.<h4>Materials & methods</h4>The plasma metabolic profile of 65 obese and 37 normal-weight children was obtained using proton NMR spectroscopy. NMR spectra were rationally divided into 110 integration regions, which reflect relative metabolite concentrations, and were used as statistical variables.<h4>Results</h4>Obese children show increased levels of lipids, N-acetyl glycoproteins ...[more]

PMID: 30057787

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Project description:BackgroundPolycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder accompanied with an increased risk of developing type 2 diabetes mellitus and cardiovascular disease; despite being a common condition, the pathogenesis of PCOS remains unclear. Our aim was to investigate the potential metabolic profiles for different phenotypes of PCOS, as well as for the early prognosis of complications.MethodsA total of 217 women with PCOS and 48 healthy women as normal controls were studied. Plasma samples of subjects were tested using two different analytical platforms of metabolomics: 1H nuclear magnetic resonance (NMR) and gas chromatography/time-of-flight mass spectrometry (GC/TOF-MS).ResultsOur results showed that carbohydrate, lipid and amino acid metabolisms were influenced in PCOS. The levels of lactate, long-chain fatty acids, triglyceride and very low-density lipoprotein were elevated, while glucose, phosphatidylcholine and high-density lipoprotein (HDL) concentrations were reduced in PCOS patients as compared with controls. Additionally, the levels of alanine, valine, serine, threonine, ornithine, phenylalanine, tyrosine and tryptophan were generally increased, whereas the levels of glycine and proline were significantly reduced in PCOS samples compared to controls. Furthermore, the ratio of branched-chain amino acid to aromatic amino acid concentrations (BCAA/AAA) in PCOS plasma was significantly reduced in PCOS patients and was insusceptible to obesity and insulin sensitivity.ConclusionsOur results suggested that the enhanced glycolysis and inhibited tricarboxylic acid cycle (TAC) in women with PCOS. Decrease of BCAA/AAA ratio was directly correlated with the development of PCOS. Ovulatory dysfunction of PCOS patients was associated with raised production of serine, threonine, phenylalanine, tyrosine and ornithine. Elevated levels of valine and leucine, and decreased concentrations of glycine in PCOS plasma could contribute to insulin sensitivity and could be considered as the potential biomarkers for long-term risk assessment of diabetes mellitus.

Project description:Childhood obesity is associated with chronic low-grade inflammation considered as a precursor to metabolic disease; however, the underlying mechanisms for this remain unclear. Studies in adults have implicated gut derived gram-negative bacterial fragments known as lipopolysaccharide or endotoxin, activating the inflammatory response, whilst the importance in childhood obesity is unclear. The aim of this research is to understand the relationship between circulating endotoxin in childhood obesity, and its' association with inflammatory and cardiovascular (CV) injury biomarkers.Fasted blood was obtained from children with varying degrees of obesity (age: 13.9 ± 2.3Yr; BMI: 35.1 ± 5.2 Kg/m(2); n = 60). Multiplex CVD biomarker immunoassays were used to determine systemic levels of inflammatory and vascular injury biomarkers, such as tumour necrosis factor-α (TNF-α), interleukin (IL-) 1β, 6, 8 and 10, plasminogen activator inhibitor-1 (PAI-1), soluble intercellular adhesion molecule type-1 (sICAM-1), matrix metalloproteinase-9 (MMP-9), myeloperoxidase (MPO) and vascular endothelial growth factor (VEGF) as well as endotoxin levels.Endotoxin levels demonstrated a significant and positive correlation with the markers for inflammation, vascular injury and atherogenesis (TNF-α: r(2) = 0.077, p < 0.05; PAI-1: r(2) = 0.215, p < 0.01; sICAM-1: r(2) = 0.159, p < 0.01; MMP-9: r(2) = 0.159, p < 0.01; MPO: r(2) = 0.07, p < 0.05; VEGF: r(2) = 0.161, p < 0.01). Males demonstrated significantly higher circulating endotoxin than females (Males: 9.63 ± 5.34 EU/ml; p = 0.004; Females: 5.56 ± 4.06 EU/ml; n = 60) in these BMI and age-matched cohorts.The present study demonstrates for the first time a significant association between circulating endotoxin and biomarkers of metabolic risk in children as young as 11 years. Thus, endotoxin-mediated sub-clinical inflammation during childhood obesity may be a key contributor to T2DM and CVD development later in life.

Dataset Information

Identification of metabolic phenotypes in childhood obesity by 1H NMR metabolomics of blood plasma.

Publications

Identification of metabolic phenotypes in childhood obesity by <sup>1</sup>H NMR metabolomics of blood plasma.

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